期刊
MOLECULAR AND CELLULAR BIOLOGY
卷 26, 期 1, 页码 362-370出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.26.1.362-370.2006
关键词
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资金
- NCI NIH HHS [P01 CA042063, P30-CA14051, P01-CA42063, P30 CA014051] Funding Source: Medline
- NIGMS NIH HHS [R37-GM34277, R37 GM034277] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [P30CA014051, P01CA042063] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R37GM034277] Funding Source: NIH RePORTER
The multiple isoforms of the transmembrane glycoprotein CD44 are produced by alternative RNA splicing. Expression of CD44 isoforms containing variable 5 exon (v5) correlates with enhanced malignancy and invasiveness of some tumors. Here we demonstrate that SRm160, a splicing coactivator, regulates CD44 alternative splicing in a Ras-dependent manner. Overexpression of SRm160 stimulates inclusion of CD44 v5 when Ras is activated. Conversely, small interfering RNA (siRNA)-mediated silencing of SRm160 significantly reduces v5 inclusion. Immunoprecipitation shows association of SRm160 with Sam68, a protein that also stimulates v5 inclusion in a Ras-dependent manner, suggesting that these two proteins interact to regulate CD44 splicing. Importantly, siRNA-mediated depletion of CD44 v5 decreases tumor cell invasion. Reduction of SRm160 by siRNA transfection downregulates the endogenous levels of CD44 isoforms, including v5, and correlates with a decrease in tumor cell invasiveness.
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